The Central Clock Neurons Regulate Lipid Storage in Drosophila

A proper balance of lipid breakdown and synthesis is essential for achieving energy homeostasis as alterations in either of these processes can lead to pathological states such as obesity. The regulation of lipid metabolism is quite complex with multiple signals integrated to control overall triglyceride levels in metabolic tissues. Based upon studies demonstrating effects of the circadian clock on metabolism, we sought to determine if the central clock cells in the Drosophila brain contribute to lipid levels in the fat body, the main nutrient storage organ of the fly. Here, we show that altering the function of the Drosophila central clock neurons leads to an increase in fat body triglycerides. We also show that although triglyceride levels are not affected by age, they are increased by expression of the amyloid-beta protein in central clock neurons. The effect on lipid storage seems to be independent of circadian clock output as changes in triglycerides are not always observed in genetic manipulations that result in altered locomotor rhythms. These data demonstrate that the activity of the central clock neurons is necessary for proper lipid storage

Recruitment of a SAP18-HDAC1 Complex into HIV-1 Virions and Its Requirement for Viral Replication

HIV-1 integrase (IN) is a virally encoded protein required for integration of viral cDNA into host chromosomes. INI1/hSNF5 is a component of the SWI/SNF complex that interacts with HIV-1 IN, is selectively incorporated into HIV-1 (but not other retroviral) virions, and modulates multiple steps, including particle production and infectivity. To gain further insight into the role of INI1 in HIV-1 replication, we screened for INI1-interacting proteins using the yeast two-hybrid system. We found that SAP18 (Sin3a associated protein 18 kD), a component of the Sin3a-HDAC1 complex, directly binds to INI1 in yeast, in vitro and in vivo. Interestingly, we found that IN also binds to SAP18 in vitro and in vivo. SAP18 and components of a Sin3A-HDAC1 complex were specifically incorporated into HIV-1 (but not SIV and HTLV-1) virions in an HIV-1 IN–dependent manner. Using a fluorescence-based assay, we found that HIV-1 (but not SIV) virion preparations harbour significant deacetylase activity, indicating the specific recruitment of catalytically active HDAC into the virions. To determine the requirement of virion-associated HDAC1 to HIV-1 replication, an inactive, transdominant negative mutant of HDAC1 (HDAC1H141A) was utilized. Incorporation of HDAC1H141A decreased the virion-associated histone deacetylase activity. Furthermore, incorporation of HDAC1H141A decreased the infectivity of HIV-1 (but not SIV) virions. The block in infectivity due to virion-associated HDAC1H141A occurred specifically at the early reverse transcription stage, while entry of the virions was unaffected. RNA-interference mediated knock-down of HDAC1 in producer cells resulted in decreased virion-associated HDAC1 activity and a reduction in infectivity of these virions. These studies indicate that HIV-1 IN and INI1/hSNF5 bind SAP18 and selectively recruit components of Sin3a-HDAC1 complex into HIV-1 virions. Furthermore, HIV-1 virion-associated HDAC1 is required for efficient early post-entry events, indicating a novel role for HDAC1 during HIV-1 replication

Regeneration Of Eggplant (Solanum Melongena L.) From Root Explants

Eggplant (Solanum melongena L.) was efficiently regenerated from cultured roots of 15-d-old seedlings on Murashige and Skoog (MS) medium containing 0.45 {\mu}M thidiazuron and 13.3 {\mu}M 6-benzyladenine. Within 28d of culture initiation, induction of organogenic calluses and subsequent differentiation into shoot buds were observed.Shoot buds upon subculture to MS basal medium elongated into healthy shoots.Excised shoots (2-4 cm) were rooted on Soilrite(R) irrigated with water either in vitro or in vivo. Plants with well-developed root systems were established under field conditions after hardening in the glasshouse, where they developed into flowering plants and produced mature fruits with viable seeds

Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity

Gregory Marslin,1 Ann Mary Revina,2,3 Vinoth Kumar Megraj Khandelwal,4 Krishnamoorthy Balakumar,5 Jose Prakash,6 Gregory Franklin,1,* Caroline J Sheeba2,3,7,*1AgroBioPlant Group, Centre for the Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Minho, Braga, Portugal; 2Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; 3ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal; 4Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy; 5Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India; 6Department of Pharmaceutics, Vels University, Chennai, Tamil Nadu, India; 7Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal*These authors contributed equally to this workAbstract: Clinical effectiveness of imatinib mesylate in cancer treatment is compromised by its off-target cardiotoxicity. In the present study, we have developed physically stable imatinib mesylate-loaded poly(lactide-co-glycolide) nanoparticles (INPs) that could sustainably release the drug, and studied its efficacy by in vitro anticancer and in vivo cardiotoxicity assays. MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay revealed that INPs are more cytotoxic to MCF-7 breast cancer cells compared to the equivalent concentration of free imatinib mesylate. Wistar rats orally administered with 50 mg/kg INPs for 28 days showed no significant cardiotoxicity or associated changes. Whereas, increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels, and reduced white blood cell, red blood cell, and hemoglobin content were observed in the animals administered with free drug. While the histological sections from hearts of animals that received INPs did not show any significant cardiotoxic symptoms, loss of normal architecture and increased cytoplasmic vacuolization were observed in the heart sections of animals administered with free imatinib mesylate. Based on these results, we conclude that nano-encapsulation of imatinib mesylate increases its efficacy against cancer cells, with almost no cardiotoxicity.Keywords: imatinib nanoparticles, cytostoxicity, cardiotoxicity, hematolog

A gradient of Bmp7 specifies the tonotopic axis in the developing inner ear

The auditory systems of animals that perceive sounds in air are organized to separate sound stimuli into their component frequencies. Individual tones then stimulate mechanosensory hair cells located at different positions on an elongated frequency (tonotopic) axis. During development, immature hair cells located along the axis must determine their tonotopic position in order to generate frequency-specific characteristics. Expression profiling along the developing tonotopic axis of the chick basilar papilla (BP) identified a gradient of Bmp7. Disruption of that gradient in vitro or in ovo induces changes in hair cell morphologies consistent with a loss of tonotopic organization and the formation of an organ with uniform frequency characteristics. Further, the effects of Bmp7 in determination of positional identity are shown to be mediated through activation of the Mapk, Tak1. These results indicate that graded, Bmp7-dependent, activation of Tak1 signaling controls the determination of frequency-specific hair cell characteristics along the tonotopic axis

Structure-function discrepancy: inhomogeneity and/ndelays in synchronized neural networks

The discrepancy between structural and functional connectivity in neural systems forms the challenge in understanding/ngeneral brain functioning. To pinpoint a mapping between structure and function, we investigated the effects of/n(in)homogeneity in coupling structure and delays on synchronization behavior in networks of oscillatory neural masses by/nderiving the phase dynamics of these generic networks. For homogeneous delays, the structural coupling matrix is largely/npreserved in the coupling between phases, resulting in clustered stationary phase distributions. Accordingly, we found only/na small number of synchronized groups in the network. Distributed delays, by contrast, introduce inhomogeneity in the/nphase coupling so that clustered stationary phase distributions no longer exist. The effect of distributed delays mimicked/nthat of structural inhomogeneity. Hence, we argue that phase (de-)synchronization patterns caused by inhomogeneous/ncoupling cannot be distinguished from those caused by distributed delays, at least not by the naked eye. The here-derived/nanalytical expression for the effective coupling between phases as a function of structural coupling constitutes a direct/nrelationship between structural and functional connectivity. Structural connectivity constrains synchronizability that may be/nmodified by the delay distribution. This explains why structural and functional connectivity bear much resemblance albeit/nnot a one-to-one correspondence. We illustrate this in the context of resting-state activity, using the anatomical/nconnectivity structure reported by Hagmann and others.This work was funded by ERC Advanced Grant: DYSTRUCTURE (n. 295129), by the Spanish Research Project SAF2010-16085 and by the CONSOLIDER-/nINGENIO 2010 Program CSD2007-00012, and the FP7-ICT BrainScal